Advertisement

Nephrotoxicity pp 353-356 | Cite as

Uptake of Cisplatin (195mPt) Into LLCPK1 Cells in the Presence of Diethyldithiocarbamate (DDTC) , Mercaptoethanesulphate (MESNA) and Amiloride

  • B. Casey
  • S. McGuinness
  • I. Pratt
  • M. P. Ryan
  • C. A. McAuliffe
  • H. L. Sharma
  • N. D. Tinker

Abstract

Cisplatin a platinum-containing co-ordination complex, is an effective antineoplastic agent used in the treatment of a variety of human malignancies including ovarian, testicular and small cell lung tumours . The clinical use of cisplatin (CP) is limited chiefly by dose-relatedcumulative nephrotoxicity which is characterised by necrosis of the S3 segment of the proximal tubule. While CP is known to accumulate in the kidney (1) , the mechanism of renal cellular accumulation is unclear although it has been suggested (2) that the drug may interact with the organic transport system in the kidney. The pars recta is notably a major site of active transport which is further support for this theory.

Keywords

Toxicity Hydration Platinum Glutamine DIETHYL 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Litterst, C.L. , 1981, Alterations in the toxicity of cisdichlorodiammine platinum II and in tissue localization of platinum as a function of NaC1 concentration in the vehicle of administration. Toxicol . Appl. Pharmacol., 61 : 99–108.PubMedCrossRefGoogle Scholar
  2. 2.
    Safirstein, R. , Miller, P. and Guttenplan, J.B., 1984, Uptake and metabolism of cisplatin by rat kidney. Kidney Int ., 25 :753–758.PubMedCrossRefGoogle Scholar
  3. 3.
    Hayes, D.M., Cvitkovic, E., Golbey, R. B., Scheiner, E., Helson, L., Krakoff, I.H., 1977, High dose cisplatinum diammine dichloride. Cancer, 39 :1372 .PubMedCrossRefGoogle Scholar
  4. 4.
    Borch, R.F. , Pleasants, M.E. , 1979, Inhibition of nephrotoxicity by diethyldithiocarbamate rescue in a rat model. Proc. Natl. Acad. Sci . USA., 76:12: 6611–6614.PubMedCrossRefGoogle Scholar
  5. 5.
    Kempf, S.R., Ivankovic, S., Wiessler, M., Schmahl, D., 1985, Effective prevention of the nephrotoxicity of cisplatin (CDDP) by administration of sodium 2-mercaptoethane-sulfonate (MESNA) in rats. Br. J. Cancer., 52: 937–939 .PubMedCrossRefGoogle Scholar
  6. 6.
    Ward, J.M. , Crabin, M.E. , Berlin, E. , Young, D.M. , 1977, Prevention of renal failure in rats receiving cisdiamminedichloroplatinum (II) by administration of furosemide. Cancer Res., 37: 1238–1240.PubMedGoogle Scholar
  7. 7.
    Rabito, C.A. , 1986, Occluding junctions in a renal cell line (LLCPK1) with characteristics of proximal tubular cells. , Am. J. Physiol. 250:F734–F743.Google Scholar
  8. 8.
    De Conti, R.C., Toftness, B.R., Lange, R.C., Creasey, W.A., 1973, Clinical and pharmacological studies with cisdiamminedichloroplatinum (II). Cancer Res ., 33: 1310–1315.Google Scholar
  9. 9.
    Ormond, T. , McGuinness, S. , Pratt, I . , Ryan, M.P. , McAuliffe, C.A. , Sharma, H.L. , Tinker, N.D. , The effecto of amiloride on cisplatin induced nephrotoxicity and the renal uptake of ( mPt) cisplatin in male Wistar rats (this volume) .Google Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • B. Casey
    • 1
  • S. McGuinness
    • 1
  • I. Pratt
    • 1
  • M. P. Ryan
    • 1
  • C. A. McAuliffe
    • 2
  • H. L. Sharma
    • 3
  • N. D. Tinker
    • 2
    • 3
  1. 1.Department of PharmacologyUniversity College DublinIreland
  2. 2.Chemistry Dept., Institute of Science and TechnologyUniversity of ManchesterManchesterEngland
  3. 3.University of ManchesterManchesterEngland

Personalised recommendations